Several studies have shown that the pulmonary toxin paraquat can modify many biological systems in the lung including DNA synthesis and repair, pyridine dinucleotide balance, glutathione status, glucose utilization and prostaglandin synthesis. Paraquat appears to be accumulated into lung tissue by a process that actively takes up endogenous polyamines. These observations suggested that paraquat may bind to similar biological sites as the polyamines, consequently modifying biochemical processes under polyamine regulation. Equilibrium dialysis and thermal denaturation studies indicated that paraquat reversibly bound to calf thymus DNA leading to a stabilization of the macromolecule. Two binding sites were apparent, defined by independent binding affinities. Putrescine only displaced paraquat from the low-affinity sites. Other studies have shown that paraquat can alter polyamine biosynthesis in vitro (100,000 g lung supernatant) by a process independent of its ability to generate toxic oxygen metabolites. Paraquat attenuated ornithine decarboxylase activity and this was reversed by the addition of putrescine. The herbicide inhibited S-adenosylmethionine decarboxylase in a dose-dependent manner and this inhibition was not altered by the addition of superoxide dismutase. The exact kinetics of paraquat interaction with DNA, ornithine decarboxylase and S-adenosylmethionine decarboxylase are presently under investigation. However, these studies suggest that paraquat is capable of competing for similar biological sites as the endogenous polyamines. Further studies using other 4,4-dipyridyl analogs both in vitro and in vivo should establish whether these compounds are useful antagonists of polyamine-regulated cellular activities.